| Human skin | |
|---|---|
 Skin of a human hand | |
 | |
| Details | |
| System | Integumentary system |
| Identifiers | |
| Latin | cutis |
| TA98 | A16.0.00.002 |
| TA2 | 7041 |
| TH | H3.12.00.1.00001 |
| FMA | 7163 |
| Anatomical terminology | |
Thehuman skin is the outer covering of the body and is the largest organ of theintegumentary system. The skin has up to seven layers ofectodermaltissue guardingmuscles,bones,ligaments andinternal organs. Human skin is similar to most of the othermammals' skin, and it is very similar topig skin. Though nearly all human skin is covered withhair follicles, it can appearhairless. There are two general types of skin: hairy andglabrous skin (hairless). The adjectivecutaneous literally means "of the skin" (from Latincutis, skin).
Skin plays an importantimmunity role in protecting the body againstpathogens and excessivewater loss. Its other functions areinsulation,temperature regulation, sensation, synthesis ofvitamin D, and the protection ofvitamin B folates. Severely damaged skin will try to heal by formingscar tissue. This is often discoloured and depigmented.
In humans,skin pigmentation (affected by melanin) varies among populations, and skin type can range fromdry to non-dry and fromoily to non-oily. Such skin variety provides a rich and diverse habitat for the approximately one thousand species ofbacteria from nineteenphyla which have been found on human skin.
Human skin shares anatomical, physiological, biochemical and immunological properties with other mammalian lines.Pig skin especially shares similar epidermal and dermal thickness ratios to human skin: pig and human skin share similar hair follicle and blood vessel patterns; biochemically the dermal collagen and elastin content is similar in pig and human skin; and pig skin and human skin have similar physical responses to various growth factors.[1][2]
Skin hasmesodermal cells which producepigmentation, such asmelanin provided bymelanocytes, which absorb some of the potentially dangerousultraviolet radiation (UV) insunlight. It containsDNA repairenzymes that help reverse UV damage. People lacking thegenes for these enzymes have high rates ofskin cancer. One form predominantly produced by UV light,malignantmelanoma, is particularly invasive, causing it tospread quickly, and can often be deadly. Human skin pigmentation varies substantially between populations; this has led to the classification of people(s) on the basis ofskin colour.[3]
In terms of surface area, the skin is the second largest organ in the human body (the inside of the small intestine is 15 to 20 times larger). For the average adult human, the skin has a surface area of 1.5–2.0 square metres (15–20 sq ft). The thickness of the skin varies considerably over all parts of the body, and between men and women, and young and old. An example is the skin on the forearm, which is on average1.3 mm in males and1.26 mm in females.[4] One average square inch (6.5 cm2) of skin holds 650 sweat glands, 20 blood vessels, 60,000 melanocytes, and more than 1,000 nerve endings.[5][better source needed] The average human skin cell is about30 μm in diameter, but there are variants. A skin cell usually ranges from 25 to 40 μm2, depending on a variety of factors.
Skin is composed of three primary layers: theepidermis, thedermis and thehypodermis.[4]
The epidermis, "epi" coming from theGreek language meaning "over" or "upon", is the outermost layer of the skin. It forms the waterproof, protective wrap over the body's surface, which also serves as a barrier toinfection and is made up of stratified squamousepithelium with an underlyingbasal lamina.
The epidermis contains noblood vessels, and cells in the deepest layers are nourished almost exclusively by diffused oxygen from the surrounding air[6] and to a far lesser degree by blood capillaries extending to the outer layers of the dermis. The main type of cells that make up the epidermis areMerkel cells,keratinocytes, withmelanocytes andLangerhans cells also present. The epidermis can be further subdivided into the followingstrata (beginning with the outermost layer): corneum, lucidum (only in palms of hands and bottoms of feet), granulosum, spinosum, and basale. Cells are formed throughmitosis at the basale layer. The daughter cells (seecell division) move up the strata changing shape and composition as they die due to isolation from their blood source. The cytoplasm is released and the proteinkeratin is inserted. They eventually reach the corneum and slough off (desquamation). This process is called"keratinization". This keratinized layer of skin is responsible for keeping water in the body and keeping other harmful chemicals andpathogens out, making skin a natural barrier to infection.[7]
The epidermis is divided into the following 5 sublayers or strata:
Blood capillaries are found beneath the epidermis and are linked to an arteriole and a venule. Arterial shunt vessels may bypass the network in ears, the nose and fingertips.
About 70% of all human protein-coding genes are expressed in the skin.[8][9] Almost 500 genes have an elevated pattern of expression in the skin. There are fewer than 100 genes that are specific for the skin, and these are expressed in the epidermis.[10] An analysis of the corresponding proteins show that these are mainly expressed inkeratinocytes and have functions related tosquamous differentiation andcornification.
The dermis is the layer of skin beneath theepidermis that consists ofconnective tissue and cushions the body from stress and strain. The dermis is tightly connected to the epidermis by abasement membrane. It also harbours manynerve endings that provide the sense of touch and heat. It contains thehair follicles,sweat glands,sebaceous glands,apocrine glands,lymphatic vessels andblood vessels. The blood vessels in the dermis provide nourishment and waste removal from its own cells as well as from the stratum basale of the epidermis.
The dermis is structurally divided into two areas: a superficial area adjacent to the epidermis, called thepapillary region, and a deep thicker area known as thereticular region.
The papillary region is composed of looseareolar connective tissue. It is named for its finger-like projections calledpapillae, which extend toward the epidermis. The papillae provide the dermis with a "bumpy" surface that interdigitates with the epidermis, strengthening the connection between the two layers of skin.
In the palms, fingers, soles, and toes, the influence of the papillae projecting into the epidermis forms contours in the skin's surface. Theseepidermal ridges occur in patterns (see:fingerprint) that are genetically andepigenetically determined and are therefore unique to the individual, making it possible to use fingerprints or footprints as a means ofidentification.
The reticular region lies deep in the papillary region and is usually much thicker. It is composed of dense irregular connective tissue, and receives its name from the dense concentration ofcollagenous,elastic, andreticular fibres that weave throughout it. Theseprotein fibres give the dermis its properties of strength, extensibility, and elasticity.
Also located within the reticular region are theroots of the hairs,sebaceous glands,sweat glands,receptors,nails, and blood vessels.
Tattoo ink is held in the dermis.Stretch marks, often from adolescent growth spurts, weight gain, pregnancy andobesity, are also located in the dermis.
Thesubcutaneous tissue (alsohypodermis andsubcutis) is not part of the skin, but lies below the dermis of thecutis. Its purpose is to attach the skin to underlying bone andmuscle as well as supplying it with blood vessels and nerves. It consists of loose connective tissue, adipose tissue andelastin. The main cell types arefibroblasts,macrophages andadipocytes (subcutaneous tissue contains 50% of body fat). Fat serves as padding and insulation for the body.
The below table identifies the skin cell count and aggregate cell mass estimates for a 70 kg adult male (ICRP-23; ICRP-89, ICRP-110).[11][12][13]
Tissue mass is defined at 3.3 kg (ICRP-89, ICRP110) and addresses the skin's epidermis, dermis, hair follicles, and glands. The cell data is extracted from 'The Human Cell Count and Cell Size Distribution',[14][15] Tissue-Table tab in the Supporting Information SO1 Dataset (xlsx). The 1200 record Dataset is supported by extensive references for cell size, cell count, and aggregate cell mass.
Detailed data for below cell groups are further subdivided into all the cell types listed in the above sections and categorized by epidermal, dermal, hair follicle, and glandular subcategories in the dataset and on the dataset's graphical website interface.[16] While adipocytes in the hypodermal adipose tissue are treated separately in the ICRP tissue categories, fat content (minus cell-membrane-lipids) resident in the dermal layer (Table-105, ICRP-23) is addressed by the below interstitial-adipocytes in the dermal layer.
| Named Tissue and Associated Cell Groups | Cell Count | Aggregate Cell Mass (g) | Percent of Total Mass |
|---|---|---|---|
| Skin Total | 6.1E+11 | 846.7 | 100% |
| Adipocyte | 7.3E+08 | 291.9 | 34.5% |
| Endothelial Cell (EnCs) | 1.5E+10 | 6.16 | 0.7% |
| Epithelial Cells (EpC) | 4.1E+11 | 313.9 | 37.1% |
| Eccrine Gland | 1.7E+11 | 105 | 12.4% |
| Epidermal Keratinocytes | 1.1E+11 | 85.5 | 10.1% |
| Hair Follicle | 1.3E+11 | 119.9 | 14.2% |
| Mechanoreceptors | 4.9E+09 | 3.6 | 0.4% |
| Epithelial Cells (EpC); Non-Nucleated | 7.2E+10 | 28.2 | 3.3% |
| Fibroblasts | 4.3E+10 | 94.6 | 11.2% |
| Myocytes | 2.6E+07 | 0.08 | 0.01% |
| Neuroglia | 8.5E+09 | 12.8 | 1.5% |
| Perivascular Cells / Pericytes / Mural | 1.5E+09 | 0.56 | 0.07% |
| Stem Cells; Epithelial (EpSC) | 3.6E+09 | 1.50 | 0.2% |
| White Blood Cells | 5.4E+10 | 97.1 | 11.5% |
| Granulocytes (Mast Cell) | 2.2E+10 | 32.6 | 3.8% |
| Lymphoid | 1.3E+10 | 1.6 | 0.2% |
| Monocyte-Macrophage Series | 1.9E+10 | 62.9 | 7.4% |
Human skin shows high skin colour variety from the darkest brown to the lightest pinkish-white hues. Human skin shows higher variation in colour than any other single mammalian species and is the result ofnatural selection. Skin pigmentation in humans evolved to primarily regulate the amount ofultraviolet radiation (UVR) penetrating the skin, controlling its biochemical effects.[17]
The actual skin colour of different humans is affected by many substances, although the single most important substance determining human skin colour is the pigmentmelanin. Melanin is produced within the skin in cells calledmelanocytes and it is the main determinant of the skin colour ofdarker-skinned humans. The skin colour of people withlight skin is determined mainly by the bluish-white connective tissue under thedermis and by thehaemoglobin circulating in the veins of the dermis. The red colour underlying the skin becomes more visible, especially in the face, when, as consequence ofphysical exercise or the stimulation of thenervous system (anger, fear),arterioles dilate.[18]
There are at least five different pigments that determine the colour of the skin.[19][20] These pigments are present at different levels and places.
There is a correlation between the geographic distribution of UV radiation (UVR) and the distribution of indigenous skin pigmentation around the world. Areas that highlight higher amounts of UVR reflect darker-skinned populations, generally located nearer towards the equator. Areas that are far from the tropics and closer to the poles have lower concentration of UVR, which is reflected in lighter-skinned populations.[21]
In the same population it has been observed that adult humanfemales are considerably lighter in skin pigmentation thanmales. Females need morecalcium duringpregnancy andlactation, andvitamin D, which is synthesized from sunlight, helps in absorbing calcium. For this reason it is thought that females may have evolved to have lighter skin in order to help their bodies absorb more calcium.[22]
TheFitzpatrick scale[23][24] is a numerical classification schema for human skin colour developed in 1975 as a way to classify the typical response of different types of skin to ultraviolet (UV) light:
| I | Always burns, never tans | Pale, Fair, Freckles |
| II | Usually burns, sometimes tans | Fair |
| III | May burn, usually tans | Light Brown |
| IV | Rarely burns, always tans | Olive brown |
| V | Moderate constitutional pigmentation | Brown |
| VI | Marked constitutional pigmentation | Black |
As skin ages, it becomes thinner and more easily damaged. Intensifying this effect is the decreasing ability of skin to heal itself as a person ages.
Among other things, skin ageing is noted by a decrease in volume and elasticity. There are manyinternal and external causes to skin ageing. For example, ageing skin receives less blood flow and lower glandular activity.
A validated comprehensive grading scale has categorized the clinical findings of skin ageing as laxity (sagging), rhytids (wrinkles), and the various facets of photoageing, includingerythema (redness), andtelangiectasia, dyspigmentation (brown discolouration), solar elastosis (yellowing), keratoses (abnormal growths) and poor texture.[25]
Cortisol causes degradation ofcollagen,[26] accelerating skin ageing.[27]
Anti-ageing supplements are used to treat skin ageing.[citation needed]
Photoageing has two main concerns: an increased risk forskin cancer and the appearance of damaged skin. In younger skin, sun damage will heal faster since the cells in theepidermis have a faster turnover rate, while in the older population the skin becomes thinner and the epidermis turnover rate for cell repair is lower, which may result in thedermis layer being damaged.[28]
UV-irradiation of human skin cells generatesdamages in DNA through directphotochemical reactions at adjacentthymine orcytosine residues on the same strand of DNA.[29] Cyclobutanepyrimidine dimers formed by two adjacent thymine bases, or by two adjacent cytosine bases, in DNA are the most frequent types of DNA damage induced by UV. Humans, as well as other organisms, are capable of repairing such UV-induced damages by the process ofnucleotide excision repair.[29] In humans this repair process protects against skin cancer.[29]
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Though most human skin is covered withhair follicles, some parts can behairless. There are two general types of skin, hairy andglabrous skin (hairless).[30] The adjectivecutaneous means "of the skin" (from Latincutis, skin).[31]
Skin performs the following functions:
The human skin is a rich environment for microbes.[34][35] Around 1,000 species ofbacteria from 19 bacterialphyla have been found.[35][34] Most come from only four phyla:Actinomycetota (51.8%),Bacillota (24.4%),Pseudomonadota (16.5%), andBacteroidota (6.3%).Propionibacteria andStaphylococci species were the main species insebaceous areas. There are three main ecological areas: moist, dry and sebaceous. In moist places on the bodyCorynebacteria together withStaphylococci dominate. In dry areas, there is a mixture of species but dominated byBetaproteobacteria andFlavobacteriales. Ecologically, sebaceous areas had greater species richness than moist and dry ones. The areas with least similarity between people in species were the spaces betweenfingers, the spaces betweentoes,axillae, andumbilical cord stump. Most similarly were beside thenostril,nares (insidethe nostril), and on the back.
Reflecting upon the diversity of the human skin researchers on the human skinmicrobiome have observed: "hairy, moist underarms lie a short distance from smooth dry forearms, but these two niches are likely as ecologically dissimilar as rainforests are to deserts."[34]
TheNIH conducted theHuman Microbiome Project to characterize the human microbiota, which includes that on the skin and the role of this microbiome in health and disease.[36]
Microorganisms likeStaphylococcus epidermidis colonize the skin surface. The density of skin flora depends on region of the skin. The disinfected skin surface gets recolonized from bacteria residing in the deeper areas of the hair follicle, gut and urogenital openings.
Diseases of the skin includeskin infections andskin neoplasms (including skin cancer).Dermatology is the branch ofmedicine that deals with conditions of the skin.[30]
There are seven cervical, twelve thoracic, five lumbar, and five sacral.[clarification needed] Certain diseases like shingles, caused by varicella-zoster infection, have pain sensations and eruptive rashes involving dermatomal distribution. Dermatomes are helpful in the diagnosis of vertebral spinal injury levels. Aside from the dermatomes, the epidermis cells are susceptible to neoplastic changes, resulting in various cancer types.[37]
The skin is also valuable for diagnosis of other conditions, since manymedical signsshow through the skin.Skin color affects the visibility of these signs, a source of misdiagnosis in unaware medical personnel.[38][39][40]
The skin supports its ownecosystems ofmicroorganisms, includingyeasts and bacteria, which cannot be removed by any amount of cleaning. Estimates place the number of individual bacteria on the surface of human skin at 7.8 million per square centimetre (50 million per square inch), though this figure varies greatly over the average 1.9 square metres (20 sq ft) of human skin. Oily surfaces, such as the face, may contain over 78 million bacteria per square centimetre (500 million per square inch). Despite these vast quantities, all of the bacteria found on the skin's surface would fit into a volume the size of a pea.[41] In general, the microorganisms keep one another in check and are part of a healthy skin. When the balance is disturbed, there may be an overgrowth and infection, such as whenantibiotics killmicrobes, resulting in an overgrowth of yeast. The skin is continuous with the innerepithelial lining of the body at the orifices, each of which supports its own complement of microbes.
Cosmetics should be used carefully on the skin because these may cause allergic reactions. Each season requires suitable clothing in order to facilitate the evaporation of the sweat. Sunlight, water and air play an important role in keeping the skin healthy.
Oily skin is caused by over-active sebaceous glands, that produce a substance calledsebum, a naturally healthy skin lubricant.[42][43] A highglycemic-index diet anddairy products (except for cheese) consumption increaseIGF-1 generation, which in turn increases sebum production.[43] Overwashing the skin does not cause sebum overproduction but may cause dryness.[43]
When the skin produces excessivesebum, it becomes heavy and thick in texture, known as oily skin.[43] Oily skin is typified by shininess, blemishes andpimples.[42] The oily-skin type is not necessarily bad, since such skin is less prone to wrinkling, or other signs of ageing,[42] because the oil helps to keep needed moisture locked into theepidermis (outermost layer of skin). The negative aspect of the oily-skin type is that oily complexions are especially susceptible to clogged pores,blackheads, and buildup of dead skin cells on the surface of the skin.[42] Oily skin can besallow and rough in texture and tends to have large, clearly visible pores everywhere, except around the eyes and neck.[42]
Human skin has a lowpermeability; that is, most foreign substances are unable to penetrate and diffuse through the skin. Skin's outermost layer, the stratum corneum, is an effective barrier to mostinorganic nanosized particles.[44][45] This protects the body from external particles such as toxins by not allowing them to come into contact with internal tissues. However, in some cases it is desirable to allow particles entry to the body through the skin. Potential medical applications of such particle transfer has prompted developments innanomedicine andbiology to increase skin permeability. One application of transcutaneous particle delivery could be to locate and treat cancer. Nanomedical researchers seek to target the epidermis and other layers of active cell division wherenanoparticles can interact directly with cells that have lost their growth-control mechanisms (cancer cells). Such direct interaction could be used to more accurately diagnose properties of specific tumours or to treat them by delivering drugs with cellular specificity.
Nanoparticles 40 nm in diameter and smaller have been successful in penetrating the skin.[46][47][48] Research confirms that nanoparticles larger than 40 nm do not penetrate the skin past the stratum corneum.[46] Most particles that do penetrate will diffuse through skin cells, but some will travel downhair follicles and reach the dermis layer.
The permeability of skin relative to different shapes of nanoparticles has also been studied. Research has shown that spherical particles have a better ability to penetrate the skin compared tooblong (ellipsoidal) particles because spheres are symmetric in all three spatial dimensions.[48] One study compared the two shapes and recorded data that showed spherical particles located deep in the epidermis and dermis whereas ellipsoidal particles were mainly found in the stratum corneum and epidermal layers.[48]Nanorods are used in experiments because of their uniquefluorescent properties but have shown mediocre penetration.
Nanoparticles of different materials have shown skin's permeability limitations. In many experiments, gold nanoparticles 40 nm in diameter or smaller are used and have shown to penetrate to the epidermis.Titanium oxide (TiO2),zinc oxide (ZnO), andsilver nanoparticles are ineffective in penetrating the skin past the stratum corneum.[45][49]Cadmium selenide (CdSe)quantum dots have proven to penetrate very effectively when they have certain properties. Because CdSe is toxic to living organisms, the particle must be covered in a surface group. An experiment comparing the permeability of quantum dots coated inpolyethylene glycol (PEG), PEG-amine, andcarboxylic acid concluded the PEG and PEG-amine surface groups allowed for the greatest penetration of particles. The carboxylic acid coated particles did not penetrate past the stratum corneum.[48]
Scientists previously believed that the skin was an effective barrier to inorganic particles. Damage from mechanical stressors was believed to be the only way to increase its permeability.[50]
Recently, simpler and more effective methods for increasing skin permeability have been developed.Ultraviolet radiation (UVR) slightly damages the surface of skin and causes a time-dependent defect allowing easier penetration of nanoparticles.[51] The UVR's high energy causes a restructuring of cells, weakening the boundary between the stratum corneum and the epidermal layer.[51][50] The damage of the skin is typically measured by thetransepidermal water loss (TEWL), though it may take 3–5 days for the TEWL to reach its peak value. When the TEWL reaches its highest value, the maximum density of nanoparticles is able to permeate the skin. While the effect of increased permeability after UVR exposure can lead to an increase in the number of particles that permeate the skin, the specific permeability of skin after UVR exposure relative to particles of different sizes and materials has not been determined.[51]
There are other methods to increase nanoparticle penetration by skin damage:tape stripping is the process in which tape is applied to skin then lifted to remove the top layer of skin;skin abrasion is done by shaving the top 5–10 μm off the surface of the skin;chemical enhancement applies chemicals such aspolyvinylpyrrolidone (PVP),dimethyl sulfoxide (DMSO), andoleic acid to the surface of the skin to increase permeability;[52][53]electroporation increases skin permeability by the application of short pulses ofelectric fields. The pulses are high voltage and on the order of milliseconds when applied.Charged molecules penetrate the skin more frequently than neutral molecules after the skin has been exposed to electric field pulses. Results have shown molecules on the order of 100 μm to easily permeate electroporated skin.[53]
A large area of interest in nanomedicine is thetransdermal patch because of the possibility of a painless application of therapeutic agents with very few side effects. Transdermal patches have been limited to administer a small number of drugs, such asnicotine, because of the limitations in permeability of the skin. Development of techniques that increase skin permeability has led to more drugs that can be applied via transdermal patches and more options for patients.[53]
Increasing the permeability of skin allows nanoparticles to penetrate and targetcancer cells. Nanoparticles along withmulti-modal imaging techniques have been used as a way to diagnose cancernon-invasively. Skin with high permeability allowed quantum dots with anantibody attached to the surface for active targeting to successfully penetrate and identify canceroustumours in mice. Tumour targeting is beneficial because the particles can be excited usingfluorescence microscopy and emit light energy and heat that will destroy cancer cells.[54]
Sunblock and sunscreen are different important skin-care products though both offer full protection from the sun.[55]
Sunblock—Sunblock is opaque and stronger than sunscreen, since it is able to block most of theUVA/UVB rays and radiation from the sun, and does not need to be reapplied several times in a day. Titanium dioxide and zinc oxide are two of the important ingredients in sunblock.[56]
Sunscreen—Sunscreen is more transparent once applied to the skin and also has the ability to protect against UVA/UVB rays, although the sunscreen's ingredients have the ability to break down at a faster rate once exposed to sunlight, and some of the radiation is able to penetrate to the skin. In order for sunscreen to be more effective it is necessary to consistently reapply and use one with a higher sun protection factor.
Vitamin A, also known asretinoids, benefits the skin by normalizingkeratinization, downregulatingsebum production, which contributes toacne, and reversing and treating photodamage, striae, andcellulite.
Vitamin D and analogues are used to downregulate the cutaneous immune system and epithelial proliferation while promoting differentiation.
Vitamin C is anantioxidant that regulates collagen synthesis, forms barrier lipids, regenerates vitamin E, and provides photoprotection.
Vitamin E is a membrane antioxidant that protects against oxidative damage and also provides protection against harmfulUV rays.[57]
Several scientific studies confirmed that changes in baseline nutritional status affects skin condition.[58]
Mayo Clinic lists foods they state help the skin: fruits and vegetables, whole-grains, dark leafy greens, nuts, and seeds.[59]
pig skin has been shown to be the most similar to human skin. Pig skin is structurally similar to human epidermal thickness and dermal-epidermal thickness ratios. Pigs and humans have similar hair follicle and blood vessel patterns in the skin. Biochemically pigs contain dermal collagen and elastic content that is more similar to humans than other laboratory animals. Finally pigs have similar physical and molecular responses to various growth factors.
Pig skin is anatomically, physiologically, biochemically and immunologically similar to human skin
